Promyelocytic leukemia nuclear bodies associate with transcriptionally active genomic regions

Author:

Wang Jayson1,Shiels Carol2,Sasieni Peter3,Wu Pei Jun1,Islam Suhail A.4,Freemont Paul S.2,Sheer Denise1

Affiliation:

1. Human Cytogenetics Laboratory, Cancer Research UK, London Research Institute, London WC2A 3PX, England, UK

2. Centre for Structural Biology, Department of Biological Sciences, Imperial College London, London SW7 2AZ, England, UK

3. Department of Epidemiology, Mathematics, and Statistics, Cancer Research UK, Wolfson Institute of Preventive Medicine, London EC1M 6BQ, England, UK

4. Structural Bioinformatics Group, Department of Biological Sciences, Imperial College London, London SW7 2AZ, England, UK

Abstract

The promyelocytic leukemia (PML) protein is aggregated into nuclear bodies that are associated with diverse nuclear processes. Here, we report that the distance between a locus and its nearest PML body correlates with the transcriptional activity and gene density around the locus. Genes on the active X chromosome are more significantly associated with PML bodies than their silenced homologues on the inactive X chromosome. We also found that a histone-encoding gene cluster, which is transcribed only in S-phase, is more strongly associated with PML bodies in S-phase than in G0/G1 phase of the cell cycle. However, visualization of specific RNA transcripts for several genes showed that PML bodies were not themselves sites of transcription for these genes. Furthermore, knock-down of PML bodies by RNA interference did not preferentially change the expression of genes closely associated with PML bodies. We propose that PML bodies form in nuclear compartments of high transcriptional activity, but they do not directly regulate transcription of genes in these compartments.

Publisher

Rockefeller University Press

Subject

Cell Biology

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